Grk2 rescuing activity requires the integrity of domains essential for its interaction with GPCRs, we speculate that Grk2 may regulate Hh pathway activity by downregulation of a GPCR.

The main novelty presented here is to show that septic shock induces cardiac hyporesponsiveness to isoproterenol by a mechanism dependent on nitric oxide and mediated by G protein-coupled receptor kinase isoform 2. Therefore, G protein-coupled receptor kinase isoform 2 inhibition may be a potential therapeutic target in sepsis-induced cardiac dysfunction.

study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as beta2AR-induced hypertrophy.

GRK2 down-regulation is cardioprotective during diet-induced obesity, reinforcing the protective effect of maintaining low levels of GRK2 under nutritional stress, and showing a role for this kinase in obesity-induced cardiac remodeling and steatosis.

The betaARKrgs peptide, but not endogenous GRK2, interacted with Galpha(q) and interfered with signaling through this G protein. These data support the development of GRK2-based therapeutic approaches to prevent hypertrophy and heart failure.

GRK2 is localized in the mitochondria and its kinase activity negatively impacts the function of this organelle by increasing superoxide levels and altering substrate utilization for energy production.

Erythropoietin seems to reverse sepsis-induced vasoplegia to NE through the preservation of alpha1D adrenoceptor mRNA/protein expression, inhibition of GRK2-mediated desensitization, and attenuation of NO overproduction in the mouse aorta.

In vitro, GRK2 inhibits Epac1-to-Rap1 signaling by phosphorylation of Epac1 at Ser-108 in the Disheveled/Egl-10/pleckstrin domain. GRK2 inhibits Epac1-mediated sensitization of Piezo2 which contributes to inflammatory mechanical hyperalgesia.

These results suggest GRK2 contributes to melanopsin deactivation, but that other mechanisms account for most of modulation of melanopsin activity in ipRGCs.

data suggest that inhibiting GRK2 could reverse an established insulin-resistant and obese phenotype

Post-MI AdipoR1 phosphorylation positively correlated with the expression level of GRK2. AdipoR1 is phosphorylatively modified and desensitized by GRK2 in failing cardiomyocytes, contributing to post-MI remodeling and HF progression.

findings indicate that the balance between mechanisms regulating vascular tone are shifted to favor vasoconstriction in the absence of GRK2 expression and that this leads to the age-dependent development of hypertension

atomic structure of GRK2 in complex with Galphaq and Gbetagamma, in which activated Galpha subunit of Gq is fully dissociated from Gbetagamma and dramatically reoriented from its position in the inactive Galphabetagamma heterotrimer [Galphaq, Gbetagamma

G protein-coupled receptor kinase 2 plays a positive role in Smoothened signaling, at least in part, through the promotion of an association between beta-arrestin 2 and Smoothened

a novel role for GRK2 as a target of TCR signaling that is responsible for TCR-induced transactivation of CXCR4 and TCR-CXCR4 complex formation that signals via PI3Kgamma/PREX1 to mediate cytokine production.

High GRK2 expression is associated with pulmonary vasoconstrictive disorders.

results reveal that the D2R can directly recruit GRK2 without G protein activation and that this mechanism may have relevance to achieving betaarr-biased signaling

Chronic/pathologic GPCR signaling elicits the interaction of the G-protein Gbetagamma subunit with GPCR kinase 2 (GRK2), targeting the receptor for internalization, scaffolding to pathologic signals, and receptor degradation. Targeting this pathologic Gbetagamma-GRK2 interaction has been suggested as a possible strategy for the treatment of HF.

A novel regulatory role of GRK2 was proposed for the ubiquitination of beta-arrestin in the context of the PKC-mediated heterologous regulation of GPCRs.

eIF3d promotes gallbladder cancer (GBC) progression mainly via eIF3d-GRK2-AKT axis and it may be used as a prognostic factor. The therapeutic targeting of eIF3d-GRK2 axis may be a potential treatment approach for GBC.

Compared to the original peptide, a modified peptide (Ac-EEMEFSEAEANMN-NH2) exhibited markedly higher affinity for GRK2, but very low affinity for GRK5, suggesting that it can be a sensitive and selective peptide for GRK2

Lowering the level of cellular FLNA caused an elevation in RalA activity and resulted in selective interference with the normal intracellular trafficking and signaling of D2R through GRK2.

Results demonstrate that GPR3 signals at the plasma membrane and can be silenced by GRK2/beta-arrestin overexpression. These results also strongly implicate the serine and/or threonine residues in the third intracellular loop in the regulation of GPR3 activity.

GRK2 is negatively related to IGF1R and IGF1R, but not GRK2, was associated with the tumour-node-metastasis stage and overall and disease-free survival in hepatocellular carcinoma.

The tyrosine-phosphorylated GRK2 mediates this inhibition by acting on the second intracellular loop of D3R.

GRK2 is overexpressed in pancreatic cancer, and might serve as a potential indicator of unfavorable prognosis.

It is a critical factor in diabetic endothelial dysfunction and plays a role in many physiological functions including regulation of G-protein-coupled receptors (GPCRs). (review)

Profil protéine Adrenergic, Beta, Receptor Kinase 1 (ADRBK1)

Profil protéine

The product of this gene phosphorylates the beta-2-adrenergic receptor and appears to mediate agonist-specific desensitization observed at high agonist concentrations. This protein is an ubiquitous cytosolic enzyme that specifically phosphorylates the activated form of the beta-adrenergic and related G-protein-coupled receptors. Abnormal coupling of beta-adrenergic receptor to G protein is involved in the pathogenesis of the failing heart.